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Xanthine oxidase interaction with vascular endothelial growth factor in human endothelial cell angiogenesis
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Kou, Baijun, Ni, Jinsong, Vatish, Manu and Singer, Donald R. J. (2008) Xanthine oxidase interaction with vascular endothelial growth factor in human endothelial cell angiogenesis. Microcirculation, Volume 15 (Number 3). pp. 251-267. doi:10.1080/1073968070165149 ISSN 1073-9688.
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Official URL: http://dx.doi.org/10.1080/1073968070165149
Abstract
Objectives: Reduced capillary density occurs early in cardiovascular diseases. Oxidant stress, is implicated in endothelial apoptosis. We investigated the effects of xanthine oxidase (XO) on endothelial survival signaling: protein kinase B/Akt, its cross-talk with p38 MAPK and apoptosis pathways, and its effect on vascular tube formation in vascular endothelial growth factor (VEGF)-simulated human umbilical vein cells.
Methods: We studied primary cultured human endothelial cells from the umbilical cord. Reactive oxygen species (ROS) production was detected by dibydroethidium staining, cell-signaling pathways by western blots, cell survival by western blots, and nuclear chromatin and angiogenesis response by MTT proliferation assay and three-dimensional Matrigel cultures.
Results: Exogenous XO increased cellular ROS production and caused superoxide-dependent inhibition of Akt phosphorylation and enhancement of p38 MAPK phosphorylation in a time- and dose-dependent mariner. In contrast, application of the XO inhibitor oxypurinol or allopurinol inhibited VEGF-stimulated Akt phosphorylation, indicating that endogenous XO promotes VEGF-induced endothelial cell (EC) survival signaling. Exogenous XO induced activation of caspase-3 and reduced expression of the anti-apoptosis protein Bcl-2. Exogenous XO also reduced EC viability, proliferation, and vascular tube formation by p38 MAPK-dependent, phospboinositide 3-kinase (P13-K) reversible mechanisms; whereas VEGF promoted EC survival by PT3-K-dependent, p38 MAPK-independent effects.
Conclusions: Exogenous XO activity is an important contributor to endothelial mechanisms for microvascular rarefaction., by modulation of cell survival signaling pathways; however, endogenons XO is necessary for maintaining EC survival.
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Reproductive Health ( - until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Neovascularization, Oxidative stress, Cellular signal transduction, Phosphorylation, Endothelial cells, Vascular endothelial growth factors, Xanthine | ||||
| Journal or Publication Title: | Microcirculation | ||||
| Publisher: | John Wiley & Sons Ltd. | ||||
| ISSN: | 1073-9688 | ||||
| Official Date: | April 2008 | ||||
| Dates: |
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| Volume: | Volume 15 | ||||
| Number: | Number 3 | ||||
| Number of Pages: | 17 | ||||
| Page Range: | pp. 251-267 | ||||
| DOI: | 10.1080/1073968070165149 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
Data sourced from Thomson Reuters' Web of Knowledge
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